Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: C17orf62

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 4 Mar 2022, 10:17 a.m. | Last Modified: 4 Mar 2022, 10:17 a.m.

Panel Version: 2.529

Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).

Created: 20 Oct 2020, 3:30 p.m. | Last Modified: 20 Oct 2020, 3:30 p.m.

Panel Version: 2.352

Comment on list classification: Changing rating from red to green. 6 Icelandic related cases with same variant, another variant identified in Saudia Arabian individual with related phenotype. Mouse model and functional studies support the role of this gene in Chronic granulomatous disease

Created: 22 Apr 2020, 3:21 p.m. | Last Modified: 22 Apr 2020, 3:21 p.m.

Panel Version: 2.123

Not associated with any disease phenotype in OMIM (under gene name of CYBC1).
C17orf62 is also known as CYBC1/EROS.

PMID: 30361506 - Arnadottir et al 2018 - in 2 brothers with chronic granulomatous disease (CGD) ( a rare primary immunodeficiency characterized by severe recurrent bacterial and fungal infections, along with manifestations of chronic granulomatous inflammation) WGS identified a homozygous loss-of-function mutation, p.Tyr2Ter, in CYBC1. A further 6 unrelated Icelandic additional homozygotes were found to have signs of CGD, manifesting as colitis, rare infections, or a severely impaired PMA-induced neutrophil oxidative burst.

PMID: 30312704 - Thomas et al 2019 - functional studies show that when human ortholog of Eros, CYBC1 is knocked out of human cells there is a lack/lower level of gp91phox and p22phox expression. These two proteins are needed for the phagocyte respiratory burst. A patient from Saudi Arabian with a homozygous CYBC1/EROS mutation who presented with fever, splenomegaly, lymphadenopathy and short stature. He was found to have a homozygous variant that affects splicing and likely results in a retained intron. The patient had undetectable levels of EROS protein compared with cells from the healthy control or the primary T cells/PBMC, while his heterozygous sister had intermediate levels.

PMID: 28351984 - Thomas et al 2017 - Eros -/- mice succumb quickly following infection with Salmonella Typhimurium or Listeria Monocytogenes. Eros is an essential regulator of the phagocyte respiratory burst.

Summary: 6 cases from Iceland with the same variant, plus another different variant found in an individual originally from Saudia Arabia. Mouse model and some functional studies.

Created: 22 Apr 2020, 3:17 p.m. | Last Modified: 22 Apr 2020, 3:17 p.m.

Panel Version: 2.120

Green List (high evidence)

Seven Icelandic families reported with same homozygous variant, p.Tyr2Ter and an additional family from different ethnic background with different homozygous splice site variant. Functional data, including mouse model. Gene also known as EROS and CYBC1 (HGNC approved name)

Created: 10 Apr 2020, 1:58 a.m. | Last Modified: 10 Apr 2020, 1:58 a.m.

Panel Version: 2.51

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Chronic granulomatous disease

Publications

• 30361506
• 30312704
• 28351984

I don't know

Added publication referenced by IUIS december 2019 update

Created: 28 Feb 2020, 8:49 p.m. | Last Modified: 28 Feb 2020, 8:49 p.m.

Panel Version: 2.36

Approved HGNC gene symbol for C17orf62 is CYBC1 (as submitted by IUIS update December 2019)

Created: 28 Feb 2020, 12:27 p.m. | Last Modified: 28 Feb 2020, 12:27 p.m.

Panel Version: 2.11

Publications

• 30361506
• 30312704